Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.34 (lipoprotein lipase)
 7,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of multicytokine inducer, OK-432, on tumor-induced metabolic alterations were studied by assessing three key regulatory enzymes of gluconeogenesis, de novo fatty acid synthesis and the triglyceride clearance pathways. Two Klinish Einheit (KE) of OK-432 was subcutaneously injected on alternate days, for 10 days, into Fischer 344 rats with or without methylcholanthrene-induced sarcoma. At the time of sacrifice, the tumors accounted for approximately 23% of their total body weight. The injections of OK-432 did not affect the amount of food intake in either the tumor bearers or the controls. The tissue lipoprotein lipase activities in the epididymal fat pads of the tumor bearers were significantly decreased compared with the controls (P < 0.01). Phosphoenolpyruvate carboxykinase activity in the liver was significantly increased (P < 0.01), while malic enzyme activity tended to be decreased in the tumor bearers compared with the controls. However, there were no significant differences in those activities depending on the OK-432 injections, even though OK-432 induced tumor necrosis factor (TNF) and increased cytotoxic activities in the mesenteric lymph nodes as well as in the spleen. Thus, although the role of monokines in inducing cancer cachexia is not yet clearly understood, OK-432 was not able to revert the tumor-induced metabolic alterations which lead to tissue wasting and cancer cachexia.
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PMID:The effects of a biological response modifier, OK-432, on tumor-induced alterations in the host metabolism. 836 14

The role of insulin resistance in the tumor-induced decrease in tissue lipoprotein lipase (LPL) activity was studied in vivo and vitro in methylcholanthrene-induced sarcoma-bearing rats. Intraperitoneal (i.p.) injection of 2U of regular insulin resulted in high-adipose LPL activity in control rats (CTR) of 122.0 +/- 42.4 U/mg tissue, but it had little effect on tumor-bearing rats (TBR), which showed a value of only 9.6 +/- 5.5 U/mg tissue (P = 0.002). When adjusted for serum insulin concentrations, adipose LPL activity remained significantly different between the TBR and CTR at 0.19 +/- 0.17 and 0.78 +/- 0.29 U/mg tissue, respectively (P = 0.02). Following the in vitro incubation with either 1.44 g/l glucose of 1 x 10-8 U insulin of adipose tissue fragments obtained from the TBR and the CTR, measurable LPL activity was maintained in the tissue from the CTR for 2 h but not in that from the TBR. These results suggest that the decreased LPL activities seen in the tumor-bearing state may be mediated by insulin resistance.
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PMID:Role of insulin resistance in decreasing lipoprotein lipase activity in tumor-bearing rats. 872 49

Four types of lipid emulsion for highly lipophilic antitumour agent RS-1541 (13-O-palmitoylrhizoxin) with mean particle diameters of 200-260 nm were prepared using soybean oil (SOY) or dioctanoyldecanoylglycerol (ODO) for the oil phase and lecithin (LEC) or polyoxyethylene-(60)-hydrogenated castor oil (HCO-60) for surfactants. The lipolysis rate of HCO-60-emulsified emulsions by lipoprotein lipase was much slower than that of LEC-emulsified emulsions. Particle sizes of emulsions incubated in plasma with the lipase for six hours were 75%, 79%, 101%, and 93% of initial values for SOY/LEC, ODO/LEC, SOY/HCO-60, and ODO/HCO-60 emulsions, respectively, showing an apparent size decrease for LEC-emulsified emulsions. In rats, uptake clearance values of SOY/LEC and ODO/LEC emulsions of RS-1541 in the reticuloendothelial system (RES) were 81.2 and 135.3 mL h(-1), respectively, and AUC values were 4.0 and 1.3 microg h mL(-1), respectively. In contrast, RES uptake clearances of HCO-60 emulsions of RS-1541 were considerably lower (4.2 mL h(-1) for SOY/HCO-60; 2.2 mL h(-1) for ODO/HCO-60), resulting in high AUC values (35.4 microg h mL(-1) for SOY/ HCO-60; 63.9 microg h mL(-1) for ODO/HCO-60). The concentrations of RS-1541 in tumour tissues after an intravenous administration of ODO/HCO-60 emulsions of RS-1541 to mice bearing solid tumour M5076 sarcoma were about ten times higher than those after the administration of SOY/LEC emulsions. These results indicate that HCO-60 emulsions, compared with conventional LEC emulsions, are more stable to lipoprotein lipase and show low uptakes by RES organs, long circulations in the plasma, and high distributions in tumours. Thus, these sterically stabilized emulsions could show potential as effective carriers for highly lipophilic antitumour agents to enhance the drug delivery in tumours.
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PMID:Lipid emulsions of palmitoylrhizoxin: effects of composition on lipolysis and biodistribution. 874 4

The activity of lipoprotein lipase (LPL), a key regulatory enzyme for triglyceride (TG) clearance from plasma, is reported to decrease as the tumor burden increases in tumor-bearing animals and patients with lung cancer; therefore, it is believed to play a key role in inducing cancer cachexia. We attempted to reverse cancer cachexia by stimulating LPL activity with an antihypertriglyceridemic drug, bezafibrate. Bezafibrate, which reduces circulating TG levels by stimulating tissue LPL activity, has been used clinically in patients with hypertriglyceridemia. Bezafibrate was administered subcutaneously to 24 rats at a dose of 30 mg/kg per day from the 8th day after tumor inoculation with methylcholanthrene-induced sarcoma until they were killed on either the 25th or 33rd day, at the precachectic and cachectic stages, respectively. The animals were divided into the following three groups: treated tumor-bearing rats (treated TBR group), untreated TBRs (untreated TBR group), and a control (CTR) group. LPL activities in both the adipose tissue and cardiac muscle were measured by the method of Nilsson-Ehle and Schotz. Both TG and nonesterified fatty acid (NEFA) became elevated as the size of the tumor increased in the TBRs; however, this increment was quantitatively less in the treated TBR group than in the untreated TBR group. The administration of bezafibrate resulted in preservation of the epididymal fat pad mass at the cachectic stage. A significant decrease in LPL activity in the epididymal fat was observed in the untreated TBR group at the cachectic stage, but this was prevented in the treated TBR group, the values being 2.97 +/- 1.37 U/whole tissue in the untreated TBR group, 4.03 +/- 1.11 in the treated TBR group, and 10.15 +/- 6.61 in the CTR group. Thus, tumor growth in the treated TBR group at the cachectic stage was significantly suppressed compared with that of the untreated TBR group. These results suggest that the decreased LPL activity that occurs in the tumor-bearing state can be stimulated by the antihyperlipidemic drug bezafibrate, which may modulate some of the tumor-bearing state can be stimulated by the antihyperlipidemic drug bezafibrate, which may modulate some of the tumor-induced metabolic alterations leading to cancer cachexia.
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PMID:Stimulation of decreased lipoprotein lipase activity in the tumor-bearing state by the antihyperlipidemic drug bezafibrate. 891 77

The purpose of this study was to explore the triacylglycerol (TG) deposition and lipoprotein lipase (LPL) activity in the adipose tissue of patients with muculoskeletal sarcoma. Subcutaneous adipose tissue was obtained from the thighs of 19 patients with musculoskeletal sarcomas (sarcoma group) and 20 patients with osteoarthritis of the hip joint (control group) at surgery. The adipose tissue was homogenized and aliquots of the homogenate were used to measure the TG content and to prepare an acetone/ether powder to measure the LPL activity. The TG content was higher, but not significantly, in the sarcoma group than in the control group. The LPL activity of the sarcoma group was significantly higher than that of the control group. The TG content of the sarcoma group correlated positively with the LPL activity. [35S]Methionine incorporation investigation showed that the rate of LPL synthesis was significantly higher in the sarcoma group than in the control group. These results indicated that LPL was up-regulated at the transcriptional/translational level, thus resulting in an increased TG deposition in the adipose tissue of patients with muculoskeletal sarcoma.
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PMID:The synthesis and activity of lipoprotein lipase in the subcutaneous adipose tissue of patients with musculoskeletal sarcomas. 1875 79

Many types of cancer cells require a supply of fatty acids (FA) for growth and survival, and interrupting de novo FA synthesis in model systems causes potent anticancer effects. We hypothesized that, in addition to synthesis, cancer cells may obtain preformed, diet-derived FA by uptake from the bloodstream. This would require hydrolytic release of FA from triglyceride in circulating lipoprotein particles by the secreted enzyme lipoprotein lipase (LPL), and the expression of CD36, the channel for cellular FA uptake. We find that selected breast cancer and sarcoma cells express and secrete active LPL, and all express CD36. We further show that LPL, in the presence of triglyceride-rich lipoproteins, accelerates the growth of these cells. Providing LPL to prostate cancer cells, which express low levels of the enzyme, did not augment growth, but did prevent the cytotoxic effect of FA synthesis inhibition. Moreover, LPL knockdown inhibited HeLa cell growth. In contrast to the cell lines, immunohistochemical analysis confirmed the presence of LPL and CD36 in the majority of breast, liposarcoma, and prostate tumor tissues examined (n = 181). These findings suggest that, in addition to de novo lipogenesis, cancer cells can use LPL and CD36 to acquire FA from the circulation by lipolysis, and this can fuel their growth. Interfering with dietary fat intake, lipolysis, and/or FA uptake will be necessary to target the requirement of cancer cells for FA.
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PMID:Lipoprotein lipase links dietary fat to solid tumor cell proliferation. 2128 54